Page 123 - Advanced Organic Chemistry Part B - Reactions & Synthesis

In the reaction of -methylthiobutanal, where the methylthio group has the potential 95
for chelation, BF gave 100% of anti product, whereas TiCl gave a 5:1 syn:anti ratio. 93
3 4
SECTION 2.1
SCH
SCH 3 Ph 3 Aldol Addition and
CH 3 + CH 2 CH 3 Ph Condensation Reactions
CH O OTMS
OH O
BF 3 100% anti
TiCl 4 5:1 syn

Chelation-controlled product is formed from reaction of -benzyloxypropanal
and the TBDMS silyl ketene acetal derived from ethyl acetate using 3% LiClO as
4
catalyst. 94
OCH Ph OTBDMS 3% LiClO 4 OCH Ph
2
2
+ CH
CH 3 CH O 2 CH Cl CH 3 CO CH
OCH 3 2 2 2 3
–30°C OTBDMS
84%
92:8 3,4-syn:anti
Recently, CH AlCl and CH AlCl have been shown to have excellent chelation
3 2
3
2
capacity. These catalysts effect chelation control with both 3-benzyloxy- and 3-(t-
butyldimethylsilyoxy)-2-methylpropanal, whereas BF leads to mainly syn product. 95
3
The reaction is believed to occur through a cationic complex, with the chloride ion
−
associated with a second aluminum as
CH AlCl . Interestingly, although TiCl 4
3 2
2
induced chelation control with the benzyloxy group, it did not do so with the TBDMS
group.
HO O HO O
CH O OTBDMS
RO Lewis Acid
+ RO C(CH ) + RO C(CH )
3 3
3 3
)
CH 3 C(CH 3 3 CH 3 CH
anti syn 3
TBDMSO
R
(CH ) C O M +
3 3
H
O
H
CH 3
chelated transition
structure
Lewis acid R = CH 2 Ph R = OTBDMS
anti:syn anti:syn
26:74 9:91
BF 3
50:50 7:93
SnCl 4
97:3 7:93
TiCl 4
CH 3 2 AlCl 90:10 97:3
78:22 77:23
CH 3 AlCl 2
93 R. Annuziata, M. Cinquini, F. Cozzi, P. G. Cozzi, and E. Consolandi, J. Org. Chem., 57, 456 (1992).
94 M. T. Reetz and D. N. A. Fox, Tetrahedron Lett., 34, 1119 (1993).
95
D. A. Evans, B. D. Allison, and M. G. Yang, Tetrahedron Lett., 40, 4457 (1999); D. A. Evans, B. D. Allison,
M. G. Yang, and C. E. Masse, J. Am. Chem. Soc., 123, 10840 (2001).